Objective To evaluate the resistance of multidrug-resistant Mycobacterium tuberculosis ( M. tb) strains to bedaquiline ( BDQ) and to analyze the relationships between their genotypes and BDQ-re-sistant phenotypes in order to provide a scientific basis for rational use of BDQ for the treatment of multidrug-resistant tuberculosis ( MDR-TB) in clinical practice. Methods A total of 387 clinical M. tb strains, inclu-ding 100 pan-susceptible strains and 287 strains isolated from patients with MDR ( MDR-TB strains) , were enrolled in this study. Of the 287 MDR-TB strains, 77 strains were collected in Chongqing in 2015 and the other strains were collected in a national drug-resistant tuberculosis survey conducted in China during 2007 to 2008. Minimum inhibitory concentrations (MIC) of BDQ against those strains were detected. Genotypes of those strains were analyzed by Spoligotyping. Differences in the resistant rates against BDQ between Beijing genotype and non-Beijng genotype MDR-TB strains were comparatively analyzed. Results MIC50 and MIC90 of BDQ against the 287 MDR-TB strains were 0. 03 μg/ml and 0. 25 μg/ml, respectively. Nineteen out of the 287 MDR-TB strains (6. 6%) were resistant to BDQ. Based on the Spoligotyping, 195 strains were clas-sified into Beijing genotype, and the other 92 strains belonged to non-Beijing genotype. Statistical analysis revealed that the BDQ-resistant rate in Being genotype strains (4. 6%, 9/195) was lower than that in non-Beijing genotype strains (10. 9%, 10/92, χ2=3. 955, P=0. 047). In addition, the MIC50 and MIC90 of BDQ against pan-susceptible strains were 0. 03 μg/ml and 0. 12 μg/ml, respectively. Sixty-three pan-sus-ceptible strains belonged to Beijing genotype and the other 37 strains belonged to non-Beijing genotype. None of the pan-susceptible strains was resistant to BDQ. Conclusion This study indicates that BDQ showed stronger in vitro antibacterial activity against the MDR-TB strains isolated in China. A correlation between non-Beijing genotype and BDQ resistance is observed in those MDR strains. MDR strains of Beijing genotype are more susceptible to BDQ than those of non-Beijing genotype.

To investigate the relationship between sex hormone binding globulin (SHBG) and metabolic syndrome in elderly males in Shanghai,all the subjects (≥ 60 years old,male) underwent measurements of weight,height,waist and hip circumferences,and blood pressures,serum levels of fasting plasma glucose,total cholesterol,triglyceride,high density lipoprotein-cholesterol (HDL-C),and low density lipoprotein-cholesterol were determined (Hitachi,7600),while the levels of serum insulin,total testosterone,and SHBG were determined by using chemiluminescence methods.Free testosterone was calculated by using the Vermeulen equation.Metabolic syndrome was defined according to the criteria of the Chinese Diabetes Society (CDS 2004).The SHBG level in the metabolic syndrome group was significantly lower than that in non-metabolic syndrome group [(40.50 ± 26.16) nmol/L vs (47.80± 20.34) nmol/L,P＜0.01].With increasing number of metabolic syndrome components,the level of SHBG became lowered progressively.The subjects were divided into four subgroups according to SHBG Quartiles.From Quartile 1 to Quartile 4,body mass index,waist-hip ratio,diastolic blood pressure,fasting plasma glucose,triglyceride,fasting insulin,homeostasis model assessment for insulin resistance(HOMA-IR),free testosterone,free androgen index,and free testosterone percentage became progressively lowered,while age and HDL-C became raised (P＜0.05).SHBG was correlated significantly with age,body mass index,waist-hip ratio,diastolic blood pressure,fasting plasma glucose,HDL-C,and triglyceride.Age,HDL-C,and body mass index remained independently associated with SHBG in the multivariate regression analysis.In a logistic regression taking metabolic syndrome as the dependent variable,SHBG and HOMA-IR were included in the final model with statistical significance.Lowered SHBG is a risk factor of metabolic syndrome in elderly males.SHBG may be an independent predictor of metabolic syndrome,but the mechanism of how SHBG is involved in the metabolic syndrome needs to be further studied.

Objective To investigate the effect of Th1/Th2 cytokines and immune state on the occurrence and familial aggregation of hepatocellular carcinoma(HCC).Methods Ninety-five members whose families have had two or even more HCC patients(high-occurrence families) were selected as the case group,by matching with the same nationality,gender,residential area,age±5 years old,95 members whose families had no any cancer were selected as the control.The level of peripheral blood Th1 type cytokines such as interferon-γ(IFN-γ),interleukin-2(IL-2) and Th2 type cytokines such as interleukin-4(IL-4),interleukin-10 (IL-10) were detected by enzyme linked immunosorbent assay(ELISA).Results There was a Th1/Th2 serum cytokine imbalance profile in members of HCC high-occurrence family.The levels of IFN-γ and IL-2 were significantly lower in members of HCC high-occurrence family than that of the controls.The levels of IL-4 and IL-10 were higher in members of HCC high-occurrence family than that of the controls.Conclusion There was a poor cellular immune state in members of HCC in the high-occurrence families.Th1 type cytokines was inhibited,and Th2 type cytokines was enhanced,so more susceptible to HBV chronic infection.It might be the mechanism of HCC occurrence and familial aggregation.

Objective To establish a rabbit model of facial skin lifting and to evaluate the skin lifting effects of absorbable soft tissue plastic belt, and to provide experimental basis for clinical application of this plastic belt.Methods 36 Japanese white rabbits were randomly divided into model control group (n=6) and plastic belt lifting group (n=30). The model control group received only facial skin resection surgery, while the plastic belt lifting group had facial skin resection and plastic belt implantation.The changes of rabbit general status, skin lifting effects, performance of plastic belt and pathological changes of subcutaneous tissue after implantation were determined during the 4 weeks after surgery. Results The rabbit skin wound was healed within 3-7 days after surgery without infection.Meanwhile, the plastic belts did not show shifting or rupture, and only whitening around the perforations was observed in the two groups.Compared with the model control group, the MA and MB distances in the plastic belt lifting group were significantly lower ( P<0.01 ) , while the biological tension of plastic belts in the facial skin lifting rabbit models was significantly increased with the extension of time after implantation (P<0.01), and the biological tension was 18.62 N at 4 weeks after transplantation. In addition, the tensile intensities of perforations and plate in the two groups were significantly reduced at 4 weeks postoperatively (P<0.01), the tensile intensity of perforations and plate in the two groups were maintained at 35.07 N and 53.31 N, respectively, and the perforations/plate tensile intensity ratio of the two groups remained unchanged during 4 weeks after transplantation ( P >0.05 ) .Moreover, the molecular weight ( Mw ) , peak molecular weight ( Mp ) , Z molecular weight (Mz) and viscosity were gradually decreased along with the time passing after implantation (P<0.01), and its dispersion Mz/Mw ratio was also gradually decreased from 2 weeks after implantation (P<0.01), and no obvious pathological changes were found after subcutaneous implantation of the plastic belts.Conclusions We have successfully established a facial skin lifting rabbit model, and the plastic belt can obviously lift the facial skin fascia system and keep intact more than 4 weeks in the body.Therefore, this plastic belt can be applied for anti-wrinkle facial soft tissue lifting against the skin damage caused by aging.

OBJECTIVETo investigate the role of sodium cromoglycate in brain protection and its effects on brain tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) expressions after global cerebral ischemia-reperfusion (IR) injury in gerbils.

METHODSTwenty-four healthy male gerbils were randomized into 3 equal groups, namely the sham-operated group with isolation of the bilateral carotid arteries but without occlusion, IR injury model group with bilateral carotid artery occlusion, and sodium cromoglycate treatment group with bilateral carotid artery occlusion and sodium cromoglycate administration at 25 mg/kg via the lingual vein as soon as the reperfusion start with another dose 1 h later. The animals were then sacrificed and the thalamus were removed, fixed in 10% formaldehyde and sliced for observation under light microscope with HE staining. The rest brain tissues were prepared into homogenate to determine the content of TNF-alpha and IL-1beta. The right hemispheres of the gerbils were measured for wet weight and dry weight to calculate the water content in the brain.

RESULTSThe water content in the brain of the gerbils in the model group was the highest among the groups, and that in sodium cromoglycate treatment group was significantly less than that of the model group (P<0.05). Microscopic examination showed the most severe brain tissue damage in the model group with also the highest TNF-alpha and IL-1beta levels in the brain. The brain TNF-alpha and IL-1beta levels in sodium cromoglycate group were significantly decreased as compared with those in the model group (P<0.05).

CONCLUSIONSodium cromoglycate can alleviate brain IR injury possibly by lowering the TNF-alpha and IL-1beta levels in the brain tissues.

Animals ; Brain Ischemia ; metabolism ; Cromolyn Sodium ; pharmacology ; Gerbillinae ; Interleukin-1beta ; metabolism ; Male ; Neuroprotective Agents ; pharmacology ; Random Allocation ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism

Base Sequence ; Formaldehyde ; chemistry ; Humans ; Molecular Sequence Data ; Oncogene Proteins, Fusion ; genetics ; Paraffin Embedding ; Proto-Oncogene Protein c-fli-1 ; genetics ; RNA, Neoplasm ; genetics ; metabolism ; RNA-Binding Protein EWS ; Reverse Transcriptase Polymerase Chain Reaction ; methods ; Rhabdomyosarcoma ; genetics ; Sarcoma, Ewing ; genetics ; Sarcoma, Synovial ; genetics ; Soft Tissue Neoplasms ; genetics ; Tissue Fixation

The efficacy and safety of recombinant tissue plasminogen activator (rtPA) need to be improved due to its low bioavailability and requirement of large dose administration.The purpose of this study was to develop a fibrin-targeted nanoparticle (NP) drug delivery system for thrombosis combination therapy.We conjugated rtPA to poly(ethylene glycol)-poly(ε-caprolactone) (PEG-PCL) nanoparticles (rtPA-NP) and investigated its physicochemical characteristics such as particle size,zeta potential,enzyme activity of conjugated rtPA and its storage stability at 4℃.The thrombolytic activity of rtPA-NP was evaluated in vitro and in vivo as well as the half-life of rtPA-NP,the properties to fibrin targeting and its influences on systemic hemostasis in vivo.The results showed that rtPA-NP equivalent to 10％ of a typical dose of rtPA could dissolve fibrin clots and were demonstrated to have a neuroprotective effect after focal cerebral ischemia as evidenced by decreased infarct volume and improved neurological deficit (P＜0.001).RtPA-NP did not influence the in vivo hemostasis or coagulation system.The half-life of conjugated rtPA was shown to be approximately 18 times longer than that of free rtPA.These experiments suggested that rtPA-conjugated PEG-PCL nanoparticles might be a promising fibrin-targeted delivery system for a combination treatment of thrombosis.

OBJECTIVETo investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin.

METHODSThe experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR.

RESULTSElectron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F.

CONCLUSIONThe potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

Animals ; Disease Models, Animal ; Fibronectins ; genetics ; metabolism ; Kidney ; drug effects ; metabolism ; ultrastructure ; Kidney Diseases ; chemically induced ; metabolism ; pathology ; Lead Poisoning ; complications ; metabolism ; pathology ; Male ; NF-kappa B ; genetics ; metabolism ; Potassium Iodide ; pharmacology ; RNA, Messenger ; genetics ; Rats ; Rats, Sprague-Dawley

The rhizome of Alpinia officinarum is a widely used Chinese herbal medicine. The essential oil in A. officinarum rhizome is mainly composed of 1, 8-cineole and other monoterpenes, as the major bioactive ingredients. In plants, monoterpenes are synthesized through the methylerythritol phosphate (MEP) pathway in the plastids, and 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR) is an enzyme catalyzing a committed step of the MEP pathway. In the present study, the full-length cDNA encoding DXR was cloned from the rhizome of A. officinarum, using homology-based RT-PCR and rapid amplification of cDNA ends (RACE) techniques. The new cDNA was designated as AoDXR and submitted to GenBank to be assigned with an accession number HQ874658. The full-length cDNA of AoDXR was 1 670 bp containing a 1 419 bp open reading frame encoding a polypeptide of 472 amino acids with a calculated molecular mass of 51.48 kDa and an isoelectric point of 6.15. Bioinformatic analyses revealed that AoDXR showed extensive homology with DXRs from other plant species and contained a conserved plastids transit peptide, a Pro-rich region and two highly conserved NADPH-binding motifs in its N-terminal region characterized by all plant DXRs. The phylogenetic analysis revealed that AoDXR belonged to angiosperm DXRs. The structural modeling of AoDXR showed that AoDXR had the typical V-shaped structure of DXR proteins. The tissue expression pattern analysis indicated that AoDXR expressed strongly in leaves, weak in rhizomes of A. officinarum. Exogenous methyl jasmonate (MeJA) could enhance the expression of AoDXR and the production of 1, 8-cineole in A. officinarum rhizomes. The cloning and characterization of AoDXR will be helpful to reveal the molecular regulation mechanism of monoterpene biosynthesis in A. officinarum and provides a candidate gene for metabolic engineering in improving the medicinal quality of A. officinarum rhizome.
Aldose-Ketose Isomerases ; genetics ; Alpinia ; chemistry ; enzymology ; genetics ; Amino Acid Sequence ; DNA, Complementary ; genetics ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Molecular Sequence Data ; Monoterpenes ; metabolism ; Phylogeny

Objective:To understand the work experiences of vaccination nurses in western China under the background of free vaccination with COVID-19 vaccine of the entire population, and provide references for these nurses to better their performance in large-scale COVID-19 vaccination.Methods:Semi-structured interviews were conducted on working experience of COVID-19 vaccination with 11 community outpatient nurses who participated in the " Second Western Immunization Planning and Health Summit Forum" held in Chongqing on April 16 to 18, 2021. The sample size was set as information saturation, and the 7-step Colaizzi analytical methods was used in data clarification and analysis.Results:Such interviews extracted three themes: difficulties and challenges, psychological experience, organization and coordination. Difficulties and challenges included shortage of nursing human resources, shortage of resources for routine vaccination, imperfect online appointments, and epidemic prevention and control risks brought by mass vaccination; psychological experience included strong sense of responsibility, accumulation of anxiety, and lack of social identity; organizational coordination included organizational and the overall integration of vaccination resources.Conclusions:Community vaccination nurses have demonstrated a high sense of responsibility and mission in the work of the COVID-19 vaccination. Software and hardware facilities should be enhanced for higher efficiency; vaccination nurses deserve more psychological assistance to help ease their tension; the localities are recommended to organize their vaccination work to fit local conditions.